Brief Report: Impact of Maintenance Pemetrexed Cessation on Clinical Outcomes of Patients With Metastatic Nonsquamous NSCLC

Introduction

Combination chemoimmunotherapy including pemetrexed and a PD(L)1 inhibitor is a common first-line systemic therapy approach for patients with metastatic nonsquamous NSCLC. Patients often discontinue maintenance pemetrexed due to adverse effects, and little is known about the impact of maintenance pemetrexed cessation on real-world progression-free survival (rwPFS) and overall survival (OS).

Methods

A total of 121 patients with stage IV or recurrent, metastatic nonsquamous NSCLC treated at Vanderbilt University Medical Center (VUMC) were included in this retrospective analysis. Patients diagnosed between July 2017 and September 2023 were included if they received maintenance pemetrexed and pembrolizumab. Patients were divided into two groups: those who stopped pemetrexed due to toxicity and those who did not. rwPFS and OS were measured from time of stage IV or metastatic diagnosis to the date of radiographic progression or death, respectively.

Results

Among patients with stage IV or recurrent, metastatic NSCLC (n = 121), who remained on maintenance pemetrexed and pembrolizumab (n = 68), the median rwPFS was 11.7 months (95% confidence interval [CI]: 7.47–not applicable [NA]) compared with 24.3 months (95% CI, 19.37–NA) among patients who stopped maintenance pemetrexed (n = 53) (p = 0.1). The median OS in the same patient groups was 25.8 months (95% CI: 13.8–NA) compared with 36.4 months (95% CI: 26.9–NA) (p = 0.15), respectively.

Conclusions

In this study of patients with metastatic nonsquamous NSCLC who received maintenance pemetrexed and pembrolizumab, patients who stopped pemetrexed due to toxicity experienced similar outcomes to those who continued with pemetrexed. The optimal duration of maintenance chemotherapy should be further evaluated in the immunotherapy era.